Method and system for cryoablating fibroadenomas

ABSTRACT

A cryosurgical system adapted for treatment of fibroadenomas within the breast of a patient. The system includes cryoprobes and a control system which operates the cryoprobes to accomplish freezing in two stages, including a high power freeze and a low power freeze.

FIELD OF THE INVENTIONS

The inventions described below relate the field of cryosurgery and thetreatment of breast disease.

BACKGROUND OF THE INVENTIONS

The methods and systems described below provide for optimal treatment offibroadenomas. A fibroadenoma is a benign tumor found in women'sbreasts. They are small, solid, round, rubbery masses that are typicallyfound in breast self-exams or mammography. Fibroadenomas are harmless,but may be painful, palpable and emotionally bothersome, and the maymask other lesions that would otherwise be visible to mammography.Fibroadenomas are removed to alleviate pain and to alleviate theemotional burden of living with a breast lump. Even when the breast lumpis confirmed to be a benign fibroadenoma, many women elect removal forthese reasons. Typically, fibroadenomas are removed by lumpectomy, whichis an open surgical procedure. Open surgical recision requires a fairlylarge incision, creates an unsightly scar on the breast and a scarinside the breast that interferes with mammography, and it requiresgeneral anesthesia.

Sanarus, Inc. has proposed cryoablation of fibro-adenomas in its PCTpublication WO0197702. As proposed in that publication, cryoablationentailed the commonly preferred double freeze-thaw cycle consisting of a6 to 15 minute freezes followed by thawing until the internal cryoprobetemperature reaches 0° C. While that procedure is useful, the proceduredescribed below provides suitable treatment with the advantages that asmaller iceball is created, it avoids ablating tissue surrounding thefibroadenoma that need not be ablated given the benign nature of thefibroadenoma, it limits the potential for damage to the skin overlyingthe fibroadenoma, and the resorption time for the ablated mass isgreatly reduced.

SUMMARY

The methods and systems described below permit treatment offibroadenomas with a minimally invasive cryosurgical procedure. Theprocedure entails use of a cryoprobe to cryoablate a fibroadenoma.Cryoablation is performed with a period of high power freezing, followedby a period of low power freezing, followed by a period of thawing, anda repetition of high power freezing and low power freezing, followed bythawing and/or warming of the cryoprobe. When accomplished withcommercially available cryoprobes such our new Visica™ cryoprobes, whichare adapted for partial duty cycle operation, the method entails aperiod of full power freezing, followed by a period of low duty cyclefreezing, followed by a period of thawing, followed by a repetition ofthese steps.

Performance of the method is facilitated by a control system that allowsa surgeon or technician to enter desired periods of full power freezingand reduced power freezing. The desired time for full power and reducedpower freezing is selected based on the size of the fibroadenoma andempirical experience, and may be preprogrammed into the system controlbox. After entry of these parameters, the system operates automaticallyto apply cooling to the fibroadenoma as desired by the surgeon. Theprogress of the cryosurgery may be monitored with ultrasound andthermocouples.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the cryosurgical procedure for treating benign tumorsin the breast.

FIG. 2 illustrates the control box and user interface for controlling acryoprobe to accomplish the cryoablation of a fibroadenoma.

FIGS. 3, 4, 5, 6 and 7 illustrate various operations of the fibroadenomacryoablation system.

FIG. 8 illustrates a fibroadenoma cryoablation system designed tooperate with predetermined cycle times.

DETAILED DESCRIPTION OF THE INVENTIONS

FIG. 1 illustrates the cryosurgical procedure for treating benign tumorsin the breast. The patient 1 and the patient's breast 2 and skin 3 ofthe breast are shown schematically. The fibroadenoma 4 is located withinthe breast, surrounded by soft tissue and fatty tissue. The fibroadenomais a well-defined, hard mass ranging in size from 3 to 40 mm indiameter. The purpose of the procedure is to form an iceball 5 (thefrozen mass of breast tissue) around the fibroadenoma, after which thenatural healing processes of the body will result in resorption of thefibroadenoma by the patient's body. The iceball is formed with acryoprobe 6, which, as illustrated, is inserted through the skin andintervening breast tissue into the fibroadenoma, so that the distal tipextends through the fibroadenoma. A gas supply hose 7 is attached to thecryoprobe and serves to supply high-pressure gas to the cryoprobe. Thecryoprobe may include a temperature sensor, which directly or indirectlymeasures the temperature of the cryoprobe. A temperature sensor 8 may beused during the surgery to monitor skin temperature, so that surgeonscan avoid causing frost-bite on the patient's skin. An ultrasound probe9 is used during the procedure to visualize the formation, growth, andmelting of the iceball that is formed within the breast when thecryoprobe is energized. The iceball is highly echogenic, so that itsformation is very clearly visualized. The image of the iceball isdisplayed on a display screen provided with the ultrasound probe. Aninsulating mass 10 of saline or other inert substance may be injectedinto the breast, between the fibroadenoma and the skin to protect theskin from freezing when the fibroadenoma is frozen.

The cryoprobe may be our Visica™ cryoprobe, a Cryocare® cryoprobe, aSeednet™ or Cryohit™ cryoprobe, or any other cryoprobe. These cryoprobesare Joule-Thomson cryoprobes which provide cooling from the expansion ofargon gas in the tip of the cryoprobe. Gas supply is typically providedat about 3000 psi, and is controlled with solenoid valves that can becycled to control the “duty cycle” of the system. Duty cycle refers tothe percentage of time that gas is supplied to the tip of the cryoprobe,expressed as a percentage, and controlled typically in ten second timeframes (so that a 50% duty cycle indicates that gas is supplied for 5seconds out of every ten second period of operation, and a 10% dutycycle indicates that gas is supplied for 1 second out of every tensecond period of operation). These cryoprobes will also effect warmingof tissue if supplied with a warming gas (helium) which warms uponexpansion in the tip of the cryoprobe. Other cryoprobes which use liquidnitrogen flowing through the probe may also be used with the procedure.The temperature probe and ultrasound probe may be of any make.

To accomplish the procedure, the cryoprobe is operated for two cycles ofhigh power freezing, low power freezing, with a thawing periodinterposed between the cycles and a warming period provided after thesecond freezing cycle. The periods of high power freezing, low powerfreezing, and thawing are selected depending on the size of thefibroadenoma. With experimentation, we have empirically determined thefollowing freeze periods for fibroadenomas of various sizes:

Fibroadenoma Longest Passive Warm Diameter Freeze Cycle 1 Thaw FreezeCycle 2 Cycle <1 cm 2 min HI Freeze,  2 min. 2 min HI Freeze, 1 min. 0min LO Freeze 0 min LO Freeze 1.0-1.5 cm 2 min HI Freeze,  6 min. 2 minHI Freeze, 1 min. 4 min LO Freeze 4 min LO Freeze 1.6-2.0 cm 3 min HIFreeze,  8 min. 3 min HI Freeze, 1 min. 5 min LO Freeze 5 min LO Freeze2.1-2.5 cm 5 min HI Freeze, 10 min. 5 min HI Freeze, 1 min. 5 min LOFreeze 5 min LO Freeze 2.6-3.0 cm 6 min HI Freeze, 10 min. 6 min HIFreeze, 1 min 4 min LO Freeze 4 min LO Freeze 3.1-3.5 cm 8 min HIFreeze, 10 min. 8 min HI Freeze, 1 min. 2 min LO Freeze 2 min LO Freeze3.6-4.0 cm 10 min HI Freeze, 10 min. 10 min HI Freeze, 1 min.  0 min LOFreeze  0 min LO Freeze

As indicated in the table, a fibroadenoma smaller than 1 cm in diameteris treated with two freezing cycles consisting of 2 minutes of highpower freezing and without a period of low power freezing, and 2 minutesof passive thawing between the freezing cycles. A fibroadenoma of 1-1.5cm diameter is treated by two cycles consisting of 2 minutes of highpower freezing, 4 minutes of low power freezing, with 6 minutes ofpassive thawing between the cycles and a 1 minute warming periodfollowing the second freeze cycle. A fibroadenoma of 1.6 to 2.0 cmdiameter is treated by two cycles consisting of 3 minutes of high powerfreezing, 5 minutes of low power freezing, with 10 minutes of passivethawing between the freezing cycles and followed by 1 minute of warmingoperation after the two freezing cycles. A fibroadenoma of 2.1 to 2.5 cmdiameter is treated by two cycles consisting of 5 minutes of high powerfreezing, 5 minutes of low power freezing, with 10 minutes of passivethawing between the freezing cycles and followed by 1 minute of warmingoperation after the two freezing cycles. A fibroadenoma of 2.6 to 3.0 cmdiameter is treated by two cycles consisting of 6 minutes of high powerfreezing, 4 minutes of low power freezing, with 10 minutes of passivethawing between the freezing cycles and followed by 1 minute of warmingoperation after the two freezing cycles. A fibroadenoma of 3.1 to 3.5 cmdiameter is treated by two cycles consisting of 8 minutes of high powerfreezing, 2 minutes of low power freezing, with 10 minutes of passivethawing between the freezing cycles and followed by 1 minute of warmingoperation after the two freezing cycles. A fibroadenoma of 3.6 to 4.0 cmdiameter is treated by two cycles consisting of 10 minutes of high powerfreezing without a period of low power freezing, with 10 minutes ofpassive thawing between the freezing cycles and followed by 1 minute ofwarming operation after the two freezing cycles. This algorithm fortreatment is sufficient for treating fibroadenomas up to 4 cm. Largerfibroadenomas may require additional procedures.

These time periods may be varied to accomplish other regimens fallingunder the general description of two freezing cycles comprising a highpower freeze and a low power freeze with a thawing period between thefreezing cycles. It is specifically contemplated that they be adjustedto account for cryoprobes of differing cooling power or cryoprobes fromdifferent manufacturers, and that the fibroadenoma size ranges becondensed or expanded as clinical experience dictates. Also, the thawingperiod may be augmented by application of warming gas to promotethawing. Particularly, low duty cycle application of thawing gas duringthe THAW period may be employed.

FIG. 2 illustrates the control box which is used to control thecryoprobes to accomplish the procedure described above. The control box21 houses the required computer, microprocessor, or other controlcircuit, the displays and operator input devices necessary to acceptoperator input and the computer controlled valves, system input devices,to control the cryoprobe according to the operator's input. The controlbox includes a gas connection 22 for connecting the gas supply hose to avalve inside the box which controls cooling gas supply to the cryoprobe.Various valves and electro-mechanical controls within the control boxcomprise a fluid supply assembly which serves to operably connect thecryoprobe to a cooling fluid source and to a warming fluid source. Thecooling fluid is preferably high-pressure argon gas, and the warmingfluid is preferably high-pressure helium gas. A cryoprobe thermocoupleconnector 23 is provided for connecting the thermocouple typicallyinstalled in the cryoprobe to the control box.

The display and input panel 24 includes the various input buttons anddisplays used by the operator. These include cryoprobe mode selectionbuttons for selecting HI and LO, THAW, or WARM operation and buttons forinput of time parameters by the operator. The buttons or associated LEDsilluminate or otherwise alter their appearance to indicate that theoperator has selected that mode for time input (in the input mode of thesystem) or to indicate the operating mode of the cryoprobe (in theoperating mode of the system). A start/stop button 25 provides a meansfor the operator to initiate the programmed sequence of cooling andthawing after inputting desired parameters. Freezing time input buttons26 provide a means for the operator to enter procedure times for theselected cryoprobe mode selection, and the operator-entered proceduretime is displayed in the procedure time display window 27 (a resetbutton 28 can be used to reset the entered procedure time, to exit theprogramming mode, or restart the computer system which controls theinterface). Temperature indication windows 29 and 30 display thecryoprobe temperature (as measured by the thermocouple in the cryoprobe)and skin temperature (as measured by the skin mounted temperature sensor8, or perhaps a thermocouple inserted under the skin). The skintemperature sensor and separate thermocouple are connected to thecontrol box through connectors 31 and 32. The connectors may beconnected to thermocouples as desired by the operator.

The test/flush button 33 controls a test function which the controlsystem is programmed to perform prior to freezing operation. Dependingthe operating mode of the system, the test/flush button, when activatedby the operator, will initiate a short period of warming gas flowsufficient to flush the probe of any moisture (10 to 20 seconds)followed by a short period of cooling gas flow (20-60 seconds)sufficient to form an iceball in water. In conjunction with thisoperation, the operator can submerge the cryoprobe tip in water andensure that the probe tip does not leak during flushing and that aniceball forms during cooling gas flow. The test iceball is then meltedso that the cryoprobe is ready for use. When the system enters thefreeze operation mode, the operator's use of the test/flush button willinitiate warming gas flow when activated by the operator. This providesthe operator with a means for interrupting cooling operation should itbe necessary to protect skin from freezing or remove the cryoprobeimmediately for any reason.

The sequence of operation of the system is illustrated in FIG. 2 andFIGS. 3 through 7. Prior to operation of the system, the operator mustdetermine the size of the fibroadenoma to be treated. Theseillustrations assume that the operator has determined that thefibroadenoma is between 1 and 1.5 cm in diameter. In FIG. 2, theoperator has started the system, and the system has entered its programmode. The operator has pushed the HI mode selection button, and thecontrol system has illuminated the HI mode selection button and will nowinterpret time entered into the procedure time as the desired time forHI mode operation. The operator then enters the desired time for HI modeoperation, and the system stores this value as the desired duration ofHI mode operation. In this case, the operator has entered 2 minutes forHI power freezing, which is the empirically pre-determined optimal HIpower freezing time for treat the 1-1.5 cm fibroadenoma. In FIG. 3, theoperator has selected the LO mode selection button and the controlsystem has illuminated the LO mode selection button and will nowinterpret time entered into the procedure time as the desired time forLO mode operation. The operator then enters the desired time for LO modeoperation, and the system stores this value as the desired duration ofLO mode operation. In this case, the operator has entered 4 minutes forLO power freezing, which is the empirically pre-determined optimal LOpower freezing time for treat the 1-1.5 cm fibroadenoma.

The next illustrated step may be accomplished by the operator, or may beaccomplished automatically by the control system. If accomplished by theoperator, then, as shown in FIG. 4, the operator selects the THAW modeselection button and the control system illuminates the THAW modeselection button and interprets the time entered by the operator intothe procedure time as the desired time for THAW mode operation. Theoperator enters the desired time for THAW mode operation, and the systemstores this value as the desired duration of THAW mode operation. Inthis case, the operator has entered 6 minutes for THAW operation, inwhich the system does not supply gas to the cryoprobe and the iceball ispermitted to thaw (which happens fairly quickly, given that the iceballis subject to body temperature and blood flow in the surroundingtissue), which is the empirically pre-determined optimal THAW time fortreat the 1-1.5 cm fibroadenoma. We currently prefer to have the systemautomatically set the THAW time, and have empirically determined that aTHAW time equal to the combined HI and LO freeze times, which in thiscase is 6 minutes, ensures complete thawing without entailing unduedelay in proceeding to the second freeze cycle. Accordingly, the controlsystem is programmed to calculate and set the THAW time based on theentered freeze times.

After the operator has entered the HI and LO freeze times (and,optionally, the THAW time), and the cryoprobe and cryoprobe thermocouplehave been connected to the control box, and the cryoprobe has beenflushed and tested, the system will accept input from the start/stopbutton 25 as the operator's input, and start freezing operations inaccordance with the operator entered parameters. If the cryoprobe isdisconnected after testing, the system will reset itself and requirereentry of freeze time parameters. This feature may incorporate a shortdelay of about 5 seconds, such that disconnection in excess of 5 secondswill result in a reset, while disconnects of less than five seconds willbe tolerated and the system will permit the operator to initiate thefreezing operation after such a short disconnection.

As shown in FIG. 5, the system indicates that it is operating in the HIfreeze mode by illuminating the HI mode selector button (or anassociated indicator). The control system provides output to theprocedure time window to show either the elapsed or remaining HI modeoperation time. The test/flush button has entered the flush mode. Thetemperature as measured at the cryoprobe thermocouple is displayed inthe cryoprobe temperature window 29 and the skin temperature (ortemperature measured by separate probe) is displayed in the skin/auxtemperature display window 8. In this illustration, a few seconds ofcooling have elapsed and the system indicates that 1 minute and 30seconds of HI mode operation remain, the cryoprobe temperature hasreached −150° C., and the skin temperature has reached +16° C. When HImode operation is complete, the system immediately enters the LO modeoperation, and the display associated with LO mode operation isillustrated in FIG. 6. In FIG. 6, the display indicates that the controlsystem has entered into the LO mode operation, and the procedure timewindow indicates that 1 minute, 59 seconds of LO mode operation isremaining. The probe temperature display will show that the probe iswarming, but the low duty cycle operation of the cryoprobe is sufficientto maintain the iceball at substantially the same size obtained in theHI mode of freezing. Cryoprobe temperature rises, as indicated, but doesnot rise above about −45° C. (in the specific system described herein)to keep the iceball cold without permitting substantial growth of theiceball (cryoprobe temperature should cycle between about −100° C. and−45° C.). In FIG. 7, the display indicates that the control system hasentered into the THAW mode of operation. The THAW mode of 6 minutes isalmost complete, and the cryoprobe temperature has risen substantially,and the skin temperature has risen to near normal (if it has cooled atall during the freezing process).

After this THAW period, the control system will repeat the HI freeze andLO freeze operations, followed by a warming operation which isautomatically set at a pre-selected period of 30 to 60 seconds.Operation in the WARM mode permits quick removal of the cryoprobe fromthe breast after the full procedure has been accomplished. The controlsystem can also be programmed to provide an alarm or visual indicationwhen the cryoprobe reaches a predetermined temperature of about +10° C.,and to shut off warming gas flow should the cryoprobe temperatureapproach the temperature which would cause additional injury to thebreast (shut off at about +30° C. will ensure that the cryoprobetemperature does not reach thermally damaging temperature of +45° C.).Operation in the WARM mode is indicated on the display panel by the WARMmode indicator. An additional feature that is programmed into thecontrol box controls the warming mode to automatically clear thecryoprobe in the case of clogging or reduced cooling gas flow. Duringcooling operations, should cooling gas flow be reduced unexpectedly (asfrom a blockage causes by freezing inside the probe), the system canidentify the blockage and clear it automatically. To do this, thecontrol system tracks the mode of operation and the expected temperatureof the cryoprobe. If the temperature should rise (or fail to drop) whencooling gas it flowing, the control system automatically stops coolinggas flow, initiates warming gas flow for a brief period, and thenre-initiates cooling gas flow (the time for cooling may be amended bythe control system to recover the time lost to clearing the blockage).The brief period of warming gas flow (15 to 90 seconds) is sufficient tomelt most ice blockages formed within the probe. Flow rate can bemonitored indirectly by sensing the temperature of the cryoprobe, or bysensing the exhaust pressure of the cryoprobe, or it may be monitoreddirectly with flow meters anywhere in the gas flow path.

FIG. 8 illustrates a system designed to operate with pre-set freezecycles. In this system, the empirically determined optimal HI freeze, LOfreeze, and THAW and WARM times associated with fibroadenomas fallingwithin selected size ranges are programmed into the control system.Input of the predetermined HI freeze and LO freeze time period will beaccomplished by means of programming the computer, microprocessor orcontrol circuit. The interface comprises mode selection buttons whichcorrespond to the selected fibroadenoma sizes, rather than freezingmodes. After measuring the fibroadenoma, the operator selects thematching button, presses the start/stop button, and the systemautomatically selects the predetermined time periods for HI, LO and THAWoperations, and operates the cryoprobe accordingly. The test/flushoperations and the WARM mode are also available in this embodiment.

The method of treatment can be implemented on cryosurgical systems ofvarying design, modified as necessary to achieve the objectives of themethod. For example, though the LO mode of operation requires a 10% dutycycle (1 second of gas flow every ten seconds) in a Cryocare® systemusing a Cryocare® probe, other systems may be limited to duty cyclesnecessary to maintain sensed iceball temperature at or below −10° C. Ifimplemented with a nitrogen powered cryoprobe, this limitation can bemet by pulsing the flow of nitrogen, or by throttling the flow ofnitrogen, to allow the iceball to warm without permitting the iceball torecede. In a Joule-Thomson system, the reduction in freezing power canbe accomplished by reducing the pressure of cooling gas supplied to theprobes, rather than providing intermittent flow of gas supplied at aconstant high pressure. The display and input panel may be implementedas shown, with digital counters and pushbutton inputs, or through atouch-screen, or through a desktop computer and computer monitor. Thus,while the preferred embodiments of the devices and methods have beendescribed in reference to the environment in which they were developed,they are merely illustrative of the principles of the inventions. Otherembodiments and configurations may be devised without departing from thespirit of the inventions and the scope of the appended claims.

We claim:
 1. A method of treating a fibroadenoma in the breast of apatient with a cryosurgical probe, said method comprising: providing acryoprobe adapted for percutaneous insertion through the skin of thebreast and into the fibroadenoma, said cryoprobe adapted to providecooling at a first power level and a second power level, where the firstpower level provides cooling to a first cryogenic temperature and thesecond power level provides cooling to a second cryogenic temperaturewhich is higher than the first cryogenic temperature; inserting thecryoprobe into the fibroadenoma; freezing the fibroadenoma by operatingthe cryoprobe at the first power level for a first period, andthereafter operating the cryoprobe at the second power level for asecond period, and thereafter operating the cryoprobe to provide thawingduring a third period, and thereafter operating the cryoprobe at thefirst power level for a fourth period, and thereafter operating thecryoprobe at the second power level for a fifth period; and wherein thethawing period corresponds to the sum of the first and second periods.2. The method of claim 1 further comprising providing warming flow tothe cryoprobe for a predetermined period after operating the cryoprobeto freeze the fibroadenoma.
 3. The method of claim 1 wherein the firstpower level provide high power freezing and the second power levelprovides low power freezing, and the low power freezing is achieved byoperating the cryoprobe at reduced duty cycle.
 4. The method of claim 1wherein the first power level provides high power freezing and thesecond power level provides low power freezing, and the low powerfreezing is achieved by operating the cryoprobe at a 10% duty cycle. 5.The method of claim 1 wherein the first power level provides high powerfreezing and the second power level provides low power freezing, and thelow power freezing is achieved by providing the cryoprobe with a reducedflow of cooling gas.
 6. The method of claim 1 wherein the first powerlevel provides high power freezing and the second power level provideslow power freezing, and the low power freezing is achieved by providingthe cryoprobe with cooling gas at a reduced pressure.
 7. The method ofclaim 1 wherein the first power level provides high power freezing andthe second power level provides low power freezing, and the freezing andthawing periods are selected based on the size of the fibroadenoma. 8.The method of claim 1 wherein the first power level provide high powerfreezing and the second power level provides low power freezing, and thefreezing and thawing periods are selected based on the size of thefibroadenoma as follows: a fibroadenoma smaller than 1 cm in diameter istreated with 2 minutes of high power freezing and without a followingperiod of low power freezing, and 2 minutes of thawing, following by 2minutes of high power freezing without a following period of low powerfreezing; a fibroadenoma of 1-1.5 cm diameter is treated with 2 minutesof high power freezing followed by 4 minutes of low power freezingfollowed 6 minutes of thawing followed by 2 minutes of high powerfreezing followed by 4 minutes of low power freezing; a fibroadenoma of1.6 to 2.0 cm diameter is treated with 3 minutes of high power freezingfollowed by 5 minutes of low power freezing followed by 10 minutes ofthawing followed by 3 minutes of high power freezing followed by 5minutes of low power freezing followed by 10 minutes of thawing; afibroadenoma of 2.1 to 2.5 cm diameter is treated with 5 minutes of highpower freezing followed by 5 minutes of low power freezing followed by10 minutes of thawing followed by 5 minutes of high power freezingfollowed by 5 minutes of low power freezing; a fibroadenoma of 2.6 to3.0 cm diameter is treated with 6 minutes of high power freezingfollowed by 4 minutes of low power freezing followed by 10 minutes ofthawing followed by 6 minutes of high power freezing followed by 4minutes of low power freezing; a fibroadenoma of 3.1 to 3.5 cm diameteris treated with 8 minutes of high power freezing followed by 2 minutesof low power freezing followed by 10 minutes of thawing followed by 8minutes of high power freezing followed by 2 minutes of low powerfreezing; and a fibroadenoma of 3.6 to 4.0 cm diameter is treated with10 minutes of high power freezing without a following period of lowpower freezing, followed with 10 minutes of thawing followed by 10minutes of high power freezing without a following period of low powerfreezing.
 9. The method of claim 1 further comprising; empiricallydetermining the optimal high power and low power freezing periods for agiven cryoprobe, and selecting the high power period and low powerperiod to correspond to the empirically determined the optimal highpower and low power freezing periods.